Lung-resident memory B cells protect against bacterial pneumonia
Kimberly A. Barker, … , Lee J. Quinton, Joseph P. Mizgerd
Kimberly A. Barker, … , Lee J. Quinton, Joseph P. Mizgerd
Published June 1, 2021
Citation Information: J Clin Invest. 2021;131(11):e141810. https://doi.org/10.1172/JCI141810.
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Research Article Immunology Pulmonology

Lung-resident memory B cells protect against bacterial pneumonia

Abstract

Lung-resident memory B cells (BRM cells) are elicited after influenza infections of mice, but connections to other pathogens and hosts — as well as their functional significance — have yet to be determined. We postulate that BRM cells are core components of lung immunity. To test this, we examined whether lung BRM cells are elicited by the respiratory pathogen pneumococcus, are present in humans, and are important in pneumonia defense. Lungs of mice that had recovered from pneumococcal infections did not contain organized tertiary lymphoid organs, but did have plasma cells and noncirculating memory B cells. The latter expressed distinctive surface markers (including CD69, PD-L2, CD80, and CD73) and were poised to secrete antibodies upon stimulation. Human lungs also contained B cells with a resident memory phenotype. In mice recovered from pneumococcal pneumonia, depletion of PD-L2+ B cells, including lung BRM cells, diminished bacterial clearance and the level of pneumococcus-reactive antibodies in the lung. These data define lung BRM cells as a common feature of pathogen-experienced lungs and provide direct evidence of a role for these cells in pulmonary antibacterial immunity.

Authors

Kimberly A. Barker, Neelou S. Etesami, Anukul T. Shenoy, Emad I. Arafa, Carolina Lyon de Ana, Nicole M.S. Smith, Ian M.C. Martin, Wesley N. Goltry, Alexander M.S. Barron, Jeffrey L. Browning, Hasmeena Kathuria, Anna C. Belkina, Antoine Guillon, Xuemei Zhong, Nicholas A. Crossland, Matthew R. Jones, Lee J. Quinton, Joseph P. Mizgerd

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Figure 7

Systemic B cell immunity may contribute to, but is not required for, serotype-independent lung antipneumococcal immunity in experienced mice.

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Systemic B cell immunity may contribute to, but is not required for, ser...
(A) Twenty-four-hour lung Sp3 burdens in naive and experienced B6 or μMT mice (2-way ANOVA, *P = 0.013, **P = 0.0004, ***P < 0.0001). (B) Weight loss after Sp3 challenge in experienced B6 and μMT mice (2-way ANOVA comparing mouse strains within each time point, n = 16 B6 and n = 9 μMT; *P = 0.0004). (C) Plasma of experienced or naive mice was used to pre-opsonize Sp3 prior to bacterial instillation in naive mice and determination of 24-hour lung CFU (Mann-Whitney U test, *P = 0.01). Twenty-four-hour lung Sp3 CFU (D; no significant differences by 2-way ANOVA) and plasma antipneumococcal antibody titers (E) were determined in experienced mice that were splenectomized or given sham surgery 3 weeks prior to Sp3 infection (for E, Mann-Whitney U test for each isotype, *P = 0.046). (F) Twenty-four-hour lung Sp3 burdens in naive and experienced mice treated 4 days prior with isotype control or anti-CD20 (2-way ANOVA, *P = 0.0024 for IgG, P = 0.0027 for anti-CD20). LoD, limit of detection.